Book of Abstracts - New Frontiers 2022

Abstracts of oral presentations

TRANSPLANTATION OF THE HEART. INNOVATIVE METHOD MITIGATING OXIDATIVE STRESS BY MOLECULAR HYDROGEN

J. Slezak 1 , M. Hulman 2 , V. Hudec 2 , J. Luptak 2 , I. Olejarova 2 , M. Ondrusek 2 , I. Gasparovic 2 , R. Sramaty 2 , B. Szeiffova Bacova 1 , M. Barancik 1 , M. Sykora 1 , L. Okruhlicova 1 , N. Tribulova 1 , R. Boli 3 , B. Kalocayova 1 , T. W. LeBaron 1,4,5 , T. Ravingerova 1 , L. Lonek 1 , M. Zalesak 1 , K. Andelova 1 , B. Kura 1 1 Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovakia; 2 Department of Cardiac Surgery, Medical Faculty of the Slovak Medical University, National Institute of Cardiovascular Diseases, Clinic of Cardiac Surgery, Bratislava, Slovakia; 3 Institute of Molecular Cardiology, University of Louisville, Louisville, USA; 4 Molecular Hydrogen Institute, Enoch City, USA; 5 Department of Kinesiology and Outdoor Recreation, Southern Utah University, Cedar City, USA Introduction: Although heart transplantation becomes a routine method of treatment, ischemic reperfusion damage to the heart after cold ischemic storage and subsequent reperfusion is the most critical part in restoring heart function as a pump. After the cold-induced ischemic asystole and cold storage, the initial reperfusion with warm oxygenated blood, increases reactive oxygen species (ROS) including highly toxic nitrosyl and the •OH radicals. Anesthetics and hyperoxia used during anesthesia, has also been shown to be involved in ROS formation and may represent an independent mortality risk factor. Moreover, often needed electric shocks and repeated defibrillations cause significant cellular destruction in the ventricular myocardium, oxidative stress, which can complicate success of transplantation producing lipid peroxides and other oxidative stress products that damage the cardiomyocytes and interfere with production of ATP by mitochondria. The intracellular movement of calcium is leading to alterations in graft function, ventricular. Methods: Administration of hydrogen gas may mitigate the injury by selectively reducing the hydroxyl radical, a primary mediator of I/RI, decrease lipid peroxidation (malondialdehyde), inflammation (TNF- α), decreased activity of native antioxidant enzymes (Superoxide dismutase, Catalase, Glutathione peroxidase), and the improved resumption of pumping activity of 3 hours cold ischemia stored and implanted pig heart. Results: Hydrogen-treated swine exhibited significantly less severe ventricular fibrillation than controls, and improved histopathology findings. Addition of 4% inhaled hydrogen gas to inspiratory gases before the heart is taken from the donor, its cold storage, and after its implantation and subsequent warming up during its reperfusion, significantly decreased oxidative stress, markers of ischemia, inflammation, and peroxidation. Conclusion: With proper precautions, hydrogen may be administered safely through conventional ventilators, in ECC oxygenators and may represent a complementary therapy that can be easily incorporated into current transplantation technique.

Keywords: heart transplantation, molecular hydrogen, oxidative stress, inflammation, pigs

Funding: This research was funded by grants from Slovak Research and Development Agency (APVV-0241-11, APVV-15-0376, APVV-19-0317), grant from the Slovak Academy of Sciences (VEGA 2/0092/22, 2/0148/22 and 2/0063/18), grant from European Union Structural funds (ITMS 26230120009), grant (2018/7838:1-26C0), and grant from Ministry of Health of The Slovak Republic (2019-CEMSAV-1).

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